Update: The following updates relating to this announcement have been issued:

September 29, 2010 (NOT-OD-11-007) - NIH to Require Use of Updated Electronic Application Forms in 2011. Adobe B1 forms are required for due dates on or after May 8, 2011.

August 16, 2010 - IMPORTANT NOTE! NIH has eliminated the error correction window for due dates of January 25, 2011 and beyond. As of January 25, all corrections
must be complete by the due date for an application to be considered on-time. See NOT-OD-10-123.

Program
Announcement (PA) Number: PA-10-035

NOTICE: Applications
submitted in response to this Funding Opportunity Announcement (FOA) for
Federal assistance must be submitted electronically through Grants.gov (http://www.grants.gov) using the SF424
Research and Related (R&R) forms and the SF424 (R&R) Application
Guide.

APPLICATIONS MAY NOT
BE SUBMITTED IN PAPER FORMAT.

This FOA must be read
in conjunction with the application guidelines included with this announcement
in Grants.gov/Apply
for Grants (hereafter called Grants.gov/Apply).

A registration process
is necessary before submission and applicants are highly encouraged to start
the process at least four (4) weeks prior to the grant submission date. See Section IV.

Purpose.This Funding Opportunity Announcement
(FOA), issued by the National Cancer Institute (NCI), and the Office of Dietary
Supplements (ODS), of the National Institutes of Health (NIH), invites research
applications to enhance our understanding about the dynamic interrelationship that
exists between bioactive food components (and/or combinations thereof) and
cancer prevention. Although much evidence exists that dietary components are
linked to cancer prevention, the interactions among dietary bioactive compounds
and food combinations remains under-investigated. Applications are encouraged
to consider either multiple dietary bioactive components, intact foods or
multiple foods utilizing physiologically relevant concentrations of the agents.
New genetic technologies may be employed to study the impact of dietary
components on complex cellular and molecular networks, as part of the effort to
better understand the basis for the multifaceted interactions of food
components with cancer prevention mechanisms. Specifically, applications that
apply new high-throughput genomic, epigenomic, proteomic, and metabolomic
technologies to prioritize molecular targets of dietary components are highly
encouraged. The sites of action that may be evaluated include carcinogen
metabolism, DNA repair, cell proliferation, apoptosis, differentiation,
hormonal regulation, energetics, inflammation, and/or angiogenesis. In
addition, applications should either evaluate multiple molecular targets within
a cancer process or multiple processes in order to prioritize which process(es)
is/are most involved in bringing about a phenotypic change. It is hoped that advances
in this area may assist in optimizing cancer prevention while minimizing
potential toxicity due to food components. The resulting information will help
define which foods or food components should be considered in isolation or in
combination when developing dietary strategies to reduce cancer risk and/or
modify tumor behavior.

Funds
Available and Anticipated Number of Awards.Awards issued under this FOA are contingent upon the
availability of funds and the submission of a sufficient number of meritorious
applications.

Budget and Project
Period.Because the nature
and scope of the proposed research will vary from application to application,
it is anticipated that the size and duration of each award will also vary. The
total amount awarded and the number of awards will depend upon the mechanism
numbers, quality, duration, and costs of the applications received.

Application Research Strategy
Length: The R01 application Research Strategy section of the PHS398 may not
exceed 12 pages, including tables, graphs, figures, diagrams, and
charts. See Table of Page
Limits.

Eligible
Project Directors/Principal Investigators (PDs/PIs).Individuals
with the skills, knowledge, and resources necessary to carry out the proposed
research are invited to work with their institution/organization to develop an
application for support. Individuals from underrepresented racial and ethnic
groups as well as individuals with disabilities are always encouraged to apply
for NIH support.

Number of
PDs/PIs. More than one PD/PI (i.e., multiple PDs/PIs), may be
designated on the application.

Number of Applications. Applicants
may submit more than one application, provided that each application is
scientifically distinct.

Resubmissions.Applicants may submit
a resubmission application, but such application must include an Introduction
addressing the previous peer review critique (Summary Statement). See new NIH
policy on resubmission (amended) applications (NOT-OD-09-003, NOT-OD-09-016).

Renewals.Applications can be
renewed by competing for additional project periods

Application
Materials.SeeSection IV.1for application materials. All applications,
including resubmission, revision and renewal, submitted for due dates January
25, 2010 and beyond, must utilize the current forms and instructions.

General
Information.For general information
on SF424 (R&R) Application and Electronic Submission, see these Web sites:

This Funding
Opportunity Announcement (FOA), issued by the National Cancer Institute (NCI), and
the Office of Dietary Supplements (ODS), of the National Institutes of Health
(NIH), invites research applications to enhance our understanding about the
dynamic interrelationship that exists between bioactive food components (and/or
combinations thereof) and cancer prevention. Although there is evidence that
dietary components are linked to cancer prevention, the interactions among
dietary bioactive compounds and food combinations remains under-investigated.
Applications are encouraged to consider either multiple dietary bioactive
components, intact foods or multiple foods utilizing physiologically relevant
concentrations of the agents. New genetic technologies may be employed to study
the impact of dietary components on complex cellular and molecular networks, as
part of the effort to better understand the basis for the multifaceted
interactions of food components with cancer prevention mechanisms.
Specifically, applications that apply new high-throughput genomic, epigenomic,
proteomic, and metabolomic technologies to prioritize molecular targets of
dietary components are highly encouraged. The sites of action that may be
evaluated include carcinogen metabolism, DNA repair, cell proliferation,
apoptosis, differentiation, hormonal regulation, energetics, inflammation,
and/or angiogenesis. In addition, applications should evaluate either multiple
molecular targets within a cancer process or multiple processes in order to
prioritize which process(es) is/are most involved in bringing about a
phenotypic change. It is hoped that advances in this area may assist in
optimizing cancer prevention while minimizing potential toxicity due to food
components. The resulting information will help define which foods or food
components should be considered in isolation or in combination when developing
dietary strategies to reduce cancer risk and/or modify tumor behavior.

Background

Diet
and Cancer.Dietary habits are being increasingly recognized as an important modifiable environmental factor that can influence cancer risk and tumor behavior. While some have
estimated that approximately 30% of all cancer cases are related to diet, the
actual percentage may be highly dependent on the dietary components and the specific
type of cancer. Epidemiologic evidence suggests that
regular consumption of fruits, vegetables, and whole
grains may reduce cancer risk in some individuals. This association
has been attributed to certain foods being rich sources of numerous bioactive compounds.
Plant foods contain a variety of components including
essential nutrients, polyunsaturated fatty acids and phytochemicals such as
glucosinolates and flavonoids,
many of which can inhibit cell proliferation and induce apoptosis, and which
may act synergistically when combined in the human diet.

Interactions of Bioactive Dietary Components.Interactions between the different components within a food
or through food combinations may explain why isolated dietary components may
not be as efficacious for cancer prevention as whole foods. A combination of wine, fish,
dark chocolate, fruits, vegetables, garlic, and almonds have been suggested to
offer special additive benefits in cardiovascular disease risk. Whether or not
these, or possibly other, food combinations offer special protection against
cancer risk and/or modify the behavior of tumors, remains to be
adequately evaluated. Some studies do suggest that combinations of foods may
offer special advantages for cancer prevention. For example, combining soy
phytochemicals and green tea extracts has been reported to be more effective in inhibiting tumor angiogenesis, reducing
estrogen receptor (ER)-alpha and lowering serum insulin-like growth factor
(IGF)-1 than when either is provided alone. The combination
of orange, apple, grape, and blueberry displayed a
combined beneficial effect on antioxidant activity. The median
effective dose (EC50) of the combination of fruits was five times lower than
the EC50 of each fruit alone, suggesting at least additive effects after the
combination of the four fruits. However, the merit of
combining foods for maximum efficacy for cancer prevention remains to be
determined. A more scientific understanding of the mechanisms and impact of bioactive food components on cancer prevention is needed before their efficacy can be evaluated.

Intracellular
Complexity of Oncogenesis.Malignant cells
are characterized by an upregulation or constitutive activation of multiple
signaling pathways that promote proliferation, inhibit apoptosis, and enable
the cells to metastasizeand stimulate angiogenesis. Furthermore, a downregulation or loss of proteins and signaling pathways that
oppose these oncogenic behaviors is commonly seen. During carcinogenesis, cells often
acquire multiple oncogenic mutations that are often functionally redundant; thus, inhibiting any single dysregulated pathway may have
only a modest impact on tumor behavior. Therefore, the
likelihood ofany single agent
or dietary component having a “magic bullet”-like impact on cancer is minimal. Targeting multiple molecular targets
that are prone to dysregulation in a given type of cancer seems to offer the
best prospect for cancer prevention. It is highly
probable that a multitude of intracellular sites/processesin tumor formationmay be simultaneously influenced by
bioactive food components, such as carcinogen
metabolism, DNA repair, cell proliferation, apoptosis, differentiation, and
angiogenesis. Therefore, given the complexity
of intracellular response to bioactive food components, it is difficult to
determine which process(es) is/are most involved in bringing about a change in
tumor incidence/behavior.Finally, since many of these processes are likely influenced by
several food components, it is necessary to obtain a better understanding of
physiologically relevant synergistic and antagonistic
interactions.

Individual
food versus their isolated constituents. There ismounting evidence that
individual foods may offer advantages over their isolated constituents, which suggests that factors within the foods may
influence the absorption, metabolism or retention of
the bioactive food components, or that multiple bioactive compounds within the food can exert additive or
synergistic effects. For example, consumption of tomato powder, but not one of
its principle components lycopene, inhibited
N-methyl-N-nitrosourea and testosterone-induced prostate cancer. A fat-soluble
extract from vegetable powder was more efficacious than b?-carotene
in inhibiting cell proliferation and inducing morphologic changes consistent
with apoptosis (i.e., cellular
shrinkage, chromatin condensation, and nuclear fragmentation) in a lung cancer
cell line. However, in other cases, the food itself may not be as
effective as its isolated components, suggesting that the food may
contain other constituents, which can attenuate the response by
modifying the absorption, metabolism, or site of action of the bioactive food constituent. Such
antagonistic components may explain the reduced ability of soy flour and
full-fat soy flakes to inhibit aberrant crypt foci compared to isolated genistein. Therefore, a more comprehensive understanding of how the food matrix and combination of
bioactive components present within food can influence cancer
prevention is needed.

Combinations of Cancer-protective Dietary Components. Strategies that use a combination of agents with distinct
molecular mechanisms, rather than individual agents, offer an exciting
opportunity for maximizing cancer prevention while minimizing toxicity. This
approach has increased our understanding of the merits of
combining drugs. Recently, dietary components have been found to exert
additive or synergistic effects with pharmaceutical agents by modifying
different molecular targets. For example, diets containing high levels of olive oil
exert a significant protective effect against development of colon tumors, an effect that is
additive with the tumor inhibitory effects of sulindac. These protective effects are possibly related to the regulation of bothexpression and activity of key proteins involved in prostaglandin-biosynthesis (COX-2) and apoptosis-induction (Bcl-2
and caspase-3) pathways. The soy isoflavone daidzen has been reported to
improve the capacity of tamoxifen to prevent mammary tumors. These additive or
synergistic relationships may relate to different
molecular targets, and thus represent a combined effect rather than a maximum response to one
cancer process.

Dietary Components
and Conventional Drugs.Dietary
components that modify the same molecular targets as drugs may allow lower
amounts of the drug to be used for cancer prevention, thereby minimizingtheir potential
adverse effects. For example, a diet enriched in omega-3 fatty
acids can inhibit COX-2 activity and have synergistic effects with low doses of
celcoxib for colon cancer prevention. Similarly,
docosohexaenoic acid (DHA) and genistein attenuated the induction of HMG-CoA
reductase activity in mevastatin-treated MCF-7 cells. These data suggests that
dietary genistein or DHA may lower the dose of statin required to achieve the
same level of reductase inhibition, thereby
decreasing the potential for adverse effects of these drugs for breast cancer
prevention. Finally, acombination of
vitamin D3 and genistein caused growth inhibition of DU145 prostate cancer
cells at lower and biologically achievable
concentrations of both compounds. Genistein
appears to potentiate the action of vitamin D3 by directly inhibiting CYP24
enzyme activity,thereby increasing the half-life of vitamin D3, which results
in a homologous up-regulation of cellular VDR levels. These effectsled to enhanced
vitamin D-mediated responses and targeted gene activation, rendering the
cells more sensitive to the growth inhibitory and pro-apoptotic signals of
vitamin D3. However, while there is increasing understanding of the synergistic combinations of drugs, our knowledge
regarding such combinations of bioactive food components remains limited.

Synergistic
Effects of Dietary Components.Dietary
components that alter multiple molecular targets within a specific biological
process or pathway have been shown to exert
synergistic effects. For example, quercetin and genistein
synergistically inhibit proliferation of ovarian carcinoma cells by modifying
different stages in the cell cycle and different signal transduction pathways. Quercetin arrests the cell cycle at the G1 and S phase
boundary whereas genistein affects the G2 and/or early M phase. Selenium and
vitamin E have been shown to have synergistic effects on the induction of apoptosis in
human prostate cancer cells. This synergy was
accounted for primarily by selenium and vitamin E modifying distinct signaling
pathways regulatingcaspase
activation. Selenium activated caspases-1 and -12, whereas vitamin E
activated caspase-9. Thus, selenium and vitamin E in combination may activate multiple molecular targets for induction of apoptosis. These studies suggest that combinations of nutrients with
different mechanisms of action can likely have synergistic effects in cancer
prevention. However, a much better understanding of how and which dietary components work in combination is criticallyneeded for better preventative strategies.

A critical unanswered question is whether there are
additive effects of different dietary components that modulate the same
molecular target. For example, both garlic
organosulfur compounds and sulforaphane, which is present in broccoli, induce
expression of detoxifying enzymes via the binding of the transcription factor
Nrf2 to the antioxidant response element (ARE), which is
located in the promoter region of related genes. These findings
imply that in the presence of ample organosulfur
compounds, sulforaphane may not have any beneficial effects. However, these
dietary components also influence other targets in addition to ARE binding, suggesting that the additive
effects of dietary compounds on phenotypic changes can be very complex.

Specific Research Objectives

The overarching goals of this FOA are to characterize thedynamic interrelationship that exists
between bioactive food components (and/or combinations thereof) and cancer prevention, and the
complex interrelationships
between dietary components with multiple sites of action in the cancer process to
maximize cancer prevention and minimize potential toxicity.

Examples of research
supported by this FOA include, but are not limited to, the following areas:

Evaluation of the possible synergy of EGCG on VEGF
expression (anti-angiogenesis) and resveratrol suppressed COX-2 activity
(anti-inflammation) on prostate cancer risk in the TRAMP model;

This
FOA will use the Research Project Grant (R01)award
mechanism.The Project Director/Principal
Investigator (PD/PI) will be solely responsible for planning, directing, and
executing the proposed project.

This FOA uses
“Just-in-Time” information concepts (see SF424 (R&R)
Application Guide). It also uses the modular as well as the non-modular budget formats
(seehttps://grants.nih.gov/grants/funding/modular/modular.htm). Specifically, a U.S. organization submitting an application with direct costs in each year of $250,000 or
less (excluding consortium Facilities and Administrative [F&A] costs)
should use the PHS398 Modular Budget component.

U.S. applicants requesting more than
$250,000 in annual direct costs and all foreign applicants must complete and
submit budget requests using the Research & Related Budget component.

2.
Funds Available

Because the nature and scope of the proposed research
will vary from application to application, it is anticipated that the size and
duration of each award will also vary. Although the financial plans of the
IC(s) provide support for this program, awards pursuant to this funding opportunity
are contingent upon the availability of funds.

Facilities and Administrative (F&A) costs
requested by consortium participants are not included in the direct cost
limitation, see NOT-OD-05-004.

The decision of whether to
apply for a grant with a single PD/PI or multiple PDs/PIs grant is the
responsibility of the investigators and applicant organizations and should be
determined by the scientific goals of the project. Applications for grants with
multiple PDs/PIs will require additional information, as outlined in the
instructions below. When considering the multiple PD/PI option, please be aware
that the structure and governance of the PD/PI leadership team as well as the
knowledge, skills and experience of the individual PDs/PIs will be factored
into the assessment of the overall scientific merit of the application.
Multiple PDs/PIs on a project share the authority and responsibility for
leading and directing the project, intellectually and logistically. Each
PD/PI is responsible and accountable to the grantee organization, or, as
appropriate, to a collaborating organization, for the proper conduct of the
project or program, including the submission of required reports. For further
information on multiple PDs/PIs, please seehttps://grants.nih.gov/grants/multi_pi.

Number
of Applications. Applicants may submit more than one application,
provided that each application is scientifically distinct.

Resubmissions. Applicants may
submit a resubmission application, but such application must include an
Introduction addressing the previous peer review critique (Summary
Statement). Beginning with applications intended for the January 25, 2009
official submission due date, all original new applications (i.e., never
submitted) and competing renewal applications will be permitted only a single
amendment (A1). See new NIH policy on resubmission (amended) applications
(NOT-OD-09-003, NOT-OD-09-016).
Original new and competing renewal applications that were submitted prior to
January 25, 2009 will be permitted two amendments (A1 and A2). For these
“grandfathered” applications, NIH expects that any A2 will be submitted no
later than January 7, 2011, and NIH will not accept A2 applications after that
date

Renewals.Applicants
may submit a renewal application.

Section IV. Application and Submission Information

To
download a SF424 (R&R) Application Package and SF424 (R&R) Application
Guide for completing the SF424 (R&R) forms for this FOA, use the “Apply for
Grant Electronically” button in this FOA or link to http://www.grants.gov/Apply/ and follow the directions provided on that Web site.

Registration:

Appropriate
registrations with Grants.gov and eRA Commons must be completed on or before
the due date in order to successfully submit an application. Several of the steps
of the registration process could take four weeks or more. Therefore,
applicants should immediately check with their business official to determine
whether their organization/institution is already registered with both Grants.gov and the Commons.
All registrations must be complete by the submission deadline for the
application to be considered “on-time” (see 3.C.1 for more information about
on-time submission).

A one-time registration
is required for institutions/organizations at both:

The individual(s) designated as
PDs/PIs on the application must be registered also in the NIH eRA Commons. In the case of multiple PDs/PIs, all PDs/PIs must be registered and be assigned
the PI role in the eRA Commons prior to the submission of the application.

Each PD/PI must
hold a PD/PI account in the Commons. Applicants should not share a Commons account for both an Authorized Organization
Representative/Signing Official (AOR/SO) role and a PD/PI role; however, if they have both a
PD/PI role and an Internet Assisted Review (IAR) role, both roles should exist
under one Commons account.

When multiple PDs/PIs are
proposed, all PDs/PIs at the applicant organization must be affiliated with
that organization. PDs/PIs located at another institution need not be
affiliated with the applicant organization, but must be affiliated with their
own organization to be able to access the Commons.

This registration/affiliation must
be done by the AOR/SO or his/her designee who is already registered in the Commons.

Both the PD(s)/PI(s)
and AOR/SO need separate accounts in the NIH eRA Commons since both are
authorized to view the application image.

Note: The registration
process is not sequential. Applicants should begin the registration processes
for both Grants.gov and eRA Commons as soon as their organization has obtained
a DUNS number. Only one DUNS number is required and the same DUNS number must
be referenced when completing Grants.gov registration, eRA Commons registration
and the SF424 (R&R) forms.

1. Request Application
Information

Applicants
must download the SF424 (R&R) application forms and the SF424 (R&R)
Application Guide for this FOA through Grants.gov/Apply.

Note: Only the forms package
directly attached to a specific FOA can be used. You will not be able to use
any other SF424 (R&R) forms (e.g., sample forms, forms from another FOA),
although some of the "Attachment" files may be useable for more than
one FOA.

Prepare all
applications using the SF424 (R&R) application forms and in accordance with
the SF424 (R&R) Application Guide for this FOA
through Grants.gov/Apply.

The SF424 (R&R)
Application Guide is critical to submitting a complete and accurate application
to NIH. Some fields within the SF424 (R&R) application components, although
not marked as mandatory, are required by NIH (e.g., the “Credential” log-in
field of the “Research & Related Senior/Key Person Profile” component must
contain the PD/PI’s assigned eRA Commons User ID). Agency-specific
instructions for such fields are clearly identified in the Application Guide.
For additional information, see “Frequently Asked Questions – Application
Guide, Electronic
Submission of Grant Applications.”

The SF424 (R&R)
application has several components. Some components are required, others are
optional. The forms package associated with this FOA in Grants.gov/APPLYincludes all applicable components, required and optional. A completed
application in response to this FOA includes the data in the following
components:

Proposed research should provide special
opportunities for furthering research programs through the use of unusual
talent, resources, populations, or environmental conditions in other countries
that are not readily available in the United States
(U.S.) or that augment existing U.S. resources.

SPECIAL
INSTRUCTIONS

Applications with
Multiple PDs/PIs

When multiple PDs/PIs
are proposed, NIH requires one PD/PI to be designated as the "Contact” PI,
who will be responsible for all communication between the PDs/PIs and the NIH,
for assembling the application materials outlined below, and for coordinating
progress reports for the project. The contact PD/PI must meet all eligibility
requirements for PD/PI status in the same way as other PDs/PIs, but has no
other special roles or responsibilities within the project team beyond those
mentioned above.

Information for the
Contact PD/PI should be entered in item 15 of the SF424 (R&R) Cover
component. All other PDs/PIs should be listed in the Research &
Related Senior/Key Person component and assigned the project role of
“PD/PI.” Please remember that all PDs/PIs must be registered in the eRA Commons prior to application submission. The Commons ID of each PD/PI must be included
in the “Credential” field of the Research & Related Senior/Key Person
component. Failure to include this data field will cause the application
to be rejected.

All projects proposing Multiple PDs/PIs will
be required to include a new section describing the leadership plan approach
for the proposed project.

Multiple
PD/PI Leadership Plan: For applications designating multiple PDs/PIs, a new
section of the Research Plan, entitled “Multiple PD/PI Leadership Plan” must be
included. A rationale for choosing a multiple PD/PI approach should be
described. The governance and organizational structure of the leadership team
and the research project should be described, and should include communication
plans, process for making decisions on scientific direction, and procedures for
resolving conflicts. The roles and administrative, technical, and
scientific responsibilities for the project or program should be delineated for
the PDs/PIs and other collaborators.

If budget allocation
is planned, the distribution of resources to specific components of the project
or the individual PDs/PIs should be delineated in the Leadership Plan. In the
event of an award, the requested allocations may be reflected in a footnote on
the Notice of Award (NoA).

Applications
Involving a Single Institution

When all PDs/PIs are
within a single institution, follow the instructions contained in the SF424
(R&R) Application Guide.

Applications
Involving Multiple Institutions

When multiple
institutions are involved, one institution must be designated as the prime
institution and funding for the other institution(s) must be requested via a
subcontract to be administered by the prime institution. When submitting a
detailed budget, the prime institution should submit its budget using the
Research & Related Budget component. All other institutions should
have their individual budgets attached separately to the Research & Related
Subaward Budget Attachment(s) Form. See Section 4.8 of the SF424 (R&R)
Application Guide for further instruction regarding the use of the subaward
budget form.

When submitting a
modular budget, the prime institution completes the PHS398 Modular Budget
component only. Information concerning the consortium/subcontract budget
is provided in the budget justification. Separate budgets for each
consortium/subcontract grantee are not required when using the Modular budget
format. See Section 5.4 of the Application Guide for further instruction
regarding the use of the PHS398 Modular Budget component.

Applications may be submitted on or after the opening date and must be
successfully received by Grants.gov no later than 5:00 p.m. local time (of the applicant
institution/organization) on the application due date(s). (See Section
IV.3.A. for all dates.) If
an application is not submitted by the due date(s) and time, the application
may be delayed in the review process or not reviewed. All applications must
meet the following criteria to be considered “on-time”:

All
registrations must be complete prior to the submission deadline

The
application must receive a Grants.gov tracking number and timestamp (or eRA
help desk ticket confirming a system issue preventing submission) by 5:00 p.m.
local time on the submission deadline date.

Any
system identified errors/warnings must be corrected and the submission process
completed within the “error correction window.”

Submission to Grants.gov is not the last step –
applicants must follow their application through to the eRA Commons to check
for errors and warnings and view their assembled application!

3.C.2 Two Day
Window to Correct eRA Identified Errors/Warnings

IMPORTANT NOTE! NIH has eliminated the error correction window for due dates of January 25, 2011 and beyond.
As of January 25, all corrections must be complete by the due date for an application to be considered on-time. See
NOT-OD-10-123.

Once an application package has been
successfully submitted through Grants.gov,NIH provides
applicants a two day error correction window to correct any eRA
identified errors or warnings before a final assembled application is created
in the eRA Commons. The standard error correction window is two (2) business
days, beginning the day after the submission deadline and excluding weekends
and standard federal holidays. All errors must be corrected to successfully
complete the submission process. Warnings will not prevent the application
from completing the submission process.

Please note that the following
caveats apply:

Initial
application submission must be “on-time.”

The
AOR/institutions is expected to enforce that application changes made within
the error correction window are restricted to those necessary to address
system-identified errors/warnings. NIH may reject any application that
includes additional changes.

Proof of “on-time” submission (e.g., Grants.gov timestamp and
tracking number) and description of all changes made within the window must be
documented in the PHS 398 Cover Letter component of the application.

3.C.3 Viewing
an Application in the eRA Commons

Once any eRA identified errors have been
addressed and the assembled application has been created in the eRA Commons, the PD/PI and
the Authorized Organization Representative/Signing Official (AOR/SO) have two
weekdays (Monday – Friday, excluding Federal holidays) to view the assembled application before it
automatically moves forward to NIH for further processing.

If everything is
acceptable, no further action is necessary. The application
will automatically move forward to the Division of Receipt and Referral in
the Center for Scientific Review for processing after two weekdays,
excluding Federal holidays.

Prior to the submission
deadline, the AOR/SO can “Reject” the assembled application and submit a
changed/corrected application within the two-day viewing window. This
option should be used if it is determined that some part of the
application was lost or did not transfer correctly during the submission
process, the AOR/SO will have the option to “Reject” the application and
submit a Changed/Corrected application. In these cases, please contact the eRA Help Desk to
ensure that the issues are addressed and corrected. Once rejected,
applicants should follow the instructions for correcting errors in Section
2.12, including the requirement for cover letters on late applications. The “Reject” feature should also be used if you determine that
warnings are applicable to your application and need to be addressed now.
Remember, warnings do not stop further application processing. If an
application submission results in warnings (but no errors), it will
automatically move forward after two weekdays if no action is taken. Some
warnings may need to be addressed later in the process.

If
the two-day window falls after the submission deadline, the AOR/SO will have
the option to “Reject” the application if, due to an eRA Commons or Grants.gov
system issue, the application does not correctly reflect the submitted
application package (e.g., some part of the application was lost or didn’t
transfer correctly during the submission process). The AOR/SO should first
contact the eRA Commons Helpdesk to confirm the system error, document the issue, and determine the best course
of action. NIH will not penalize the applicant for an eRA Commons or Grants.gov system issue.

If
the AOR/SO chooses to “Reject” the image after the submission deadline for a
reason other than an eRA Commons or Grants.gov system failure, a
changed/corrected application still can be submitted, but it will be subject to
the NIH
late policy guidelines and may not be accepted. The reason for this delay
should be explained in the cover letter attachment.

Both
the AOR/SO and PD/PI will receive e-mail notifications when the application is
rejected or the application automatically moves forward in the process after
two weekdays.

Upon receipt, applications will be evaluated for
completeness by the Center for Scientific Review, NIH.
Incomplete applications will not be reviewed.

There
will be an acknowledgement of receipt of applications from Grants.gov and the Commons. The submitting AOR/SO
receives the Grants.gov acknowledgments. The AOR/SO and the PI receive Commons acknowledgments. Information related to the assignment of an application to a Scientific
Review Group is also in the Commons.

Note: Since email can be
unreliable, it is the responsibility of the applicant to check periodically on
their application status in the Commons.

The NIH will not
accept any application in response to this FOA that is essentially the same as
one currently pending initial merit review unless the applicant withdraws the
pending application. The NIH will not accept any application that is
essentially the same as one already reviewed. However, the NIH will accept a
resubmission application, but such application must include an Introduction
addressing the critique from the previous review.

All NIH awards are subject to the terms and conditions, cost
principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award
costs are allowable. A grantee may, at its own risk and without NIH prior
approval, incur obligations and expenditures to cover costs up to 90 days
before the beginning date of the initial budget period of a new or renewal
award if such costs: 1) are necessary to conduct the project, and 2) would be
allowable under the grant, if awarded, without NIH prior approval. If specific
expenditures would otherwise require prior approval, the grantee must obtain
NIH approval before incurring the cost. NIH prior approval is required for any
costs to be incurred more than 90 days before the beginning date of the initial
budget period of a new or renewal award.

The incurrence
of pre-award costs in anticipation of a competing or non-competing award
imposes no obligation on NIH either to make the award or to increase the amount
of the approved budget if an award is made for less than the amount anticipated
and is inadequate to cover the pre-award costs incurred. NIH expects the
grantee to be fully aware that pre-award costs result in borrowing against
future support and that such borrowing must not impair the grantee's ability to
accomplish the project objectives in the approved time frame or in any way
adversely affect the conduct of the project. See NIH Grants Policy Statement https://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm.

The
applicant organization must include its DUNS number in its Organization Profile
in the eRA Commons. This DUNS number must match the DUNS number provided at CCR
registration with Grants.gov. For
additional information, see “Frequently Asked Questions – Application Guide, Electronic
Submission of Grant Applications.”

PHS398 Research Plan Component
Sections

The
Research Strategy section of the R01 application may not exceed 12 pages, including tables, graphs, figures, diagrams, and charts. See Table of Page
Limits

All
application instructions outlined in the SF424 (R&R) Application Guide are
to be followed, incorporating "Just-in-Time" information concepts,
and with the following additional requirements:

Specific Instructions for Applications
Requesting $500,000 (direct costs) or More per Year

Applicants requesting
$500,000 or more in direct costs for any year (excluding consortium F&A
costs) must carry out the following steps:

1) Contact the IC program staff at least 6 weeks
before submitting the application, i.e., as plans are being developed for the
study;

2) Obtain agreement
from the IC staff that the IC will accept the application for consideration for
award; and,

3) Include a cover letter with the application that
identifies the staff member and IC who agreed to accept assignment of the
application.

This
policy applies to all new, renewal, revision, or resubmission applications. See NOT-OD-02-004,
October 16, 2001.

Do
not use the Appendix to circumvent the page limitations. An application that
does not comply with the required page limitations may be delayed in the review
process.

Resource Sharing Plan(s)

NIH
considers the sharing of unique research resources developed through
NIH-sponsored research an important means to enhance the value and further the
advancement of the research. When resources have been developed with NIH funds
and the associated research findings published or provided to NIH, it is
important that they be made readily available for research purposes to
qualified individuals within the scientific community. If the final data/resources are not amenable to sharing,
this must be explained in the Resource Sharing section of the application (see https://grants.nih.gov/grants/policy/data_sharing/data_sharing_faqs.htm.)

(b) Sharing Model Organisms:
Regardless of the amount requested, all applications in which the development
of model organisms is anticipated are expectedto include a
description of a specific plan for sharing and distributing unique model
organisms and related resources, or state appropriate reasons why such sharing
is restricted or not possible (see Sharing
Model Organisms Policy, and NIH
Guide NOT-OD-04-042.)

(c) Genome-Wide Association Studies (GWAS): Regardless of the amount requested, applicants seeking funding for a
genome-wide association study are expected to provide a plan for
submission of GWAS data to the NIH-designatedGWAS data
repository, or provide an appropriate explanation why submission to the
repository is not possible. A genome-wide association study is defined as
any study of genetic variation across the entire genome that is designed to
identify genetic associations with observable traits (e.g., blood pressure or
weight) or the presence or absence of a disease or condition. For further
information see Policy
for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide
Association Studies(NOT-OD-07-088) and https://grants.nih.gov/grants/gwas/.

Section V. Application Review Information

1.
Criteria

Only
the review criteria described below will be considered in the review process.

2. Review and
Selection Process

Review Process

Applications
submitted for this funding opportunity will be assigned on the basis of
established PHS referral guidelines to the ICs for funding consideration.

Applications
that are complete will be evaluated for scientific and technical merit by (an)
appropriate scientific review group(s) in accordance
with NIH peer review procedures (http://grants1.nih.gov/grants/peer/) using the review criteria stated below.

The mission of the NIH is to support science
in pursuit of knowledge about the biology and behavior of living systems and to
apply that knowledge to extend healthy life and reduce the burdens of illness
and disability. As part of this mission, applications submitted to the
NIH for grants or cooperative agreements to support biomedical and behavioral
research are evaluated for scientific and technical merit through the NIH peer
review system.

Overall
Impact. Reviewers will provide an overall impact/priority
score to reflect their assessment of the likelihood for the project to exert a
sustained, powerful influence on the research field(s) involved, in consideration
of the following five core review criteria, and additional review criteria (as
applicable for the project proposed).

Core Review
Criteria. Reviewers will consider each of the five
review criteria below in the determination of scientific and technical merit,
and give a separate score for each. An application does not need to be strong
in all categories to be judged likely to have major scientific impact. For
example, a project that by its nature is not innovative may be essential to
advance a field.

Significance. Does the project address an important problem or a
critical barrier to progress in the field? If the aims of the project are
achieved, how will scientific knowledge, technical capability, and/or clinical
practice be improved? How will successful completion of the aims change the
concepts, methods, technologies, treatments, services, or preventative
interventions that drive this field?

Investigator(s). Are the PD/PIs, collaborators, and other
researchers well suited to the project? If Early Stage Investigators or New
Investigators, do they have appropriate experience and training? If
established, have they demonstrated an ongoing record of accomplishments that
have advanced their field(s)? If the project is collaborative or multi-PD/PI,
do the investigators have complementary and integrated expertise; are their
leadership approach, governance and organizational structure appropriate for
the project?

Innovation. Does the application challenge and seek to shift current
research or clinical practice paradigms by utilizing novel theoretical
concepts, approaches or methodologies, instrumentation, or interventions? Are
the concepts, approaches or methodologies, instrumentation, or interventions
novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical
concepts, approaches or methodologies, instrumentation, or interventions
proposed?

Approach. Are the overall strategy, methodology, and analyses
well-reasoned and appropriate to accomplish the specific aims of the project? Are
potential problems, alternative strategies, and benchmarks for success
presented? If the project is in the early stages of development, will the
strategy establish feasibility and will particularly risky aspects be managed?
If the project involves clinical research, are the plans for 1) protection of
human subjects from research risks, and 2) inclusion of minorities and members
of both sexes/genders, as well as the inclusion of children, justified in terms
of the scientific goals and research strategy proposed?

Environment. Will the scientific environment
in which the work will be done contribute to the probability of success? Are
the institutional support, equipment and other physical resources available to
the investigators adequate for the project proposed? Will the project benefit
from unique features of the scientific environment, subject populations, or
collaborative arrangements?

Additional
Review Criteria

As applicable
for the project proposed, reviewers will consider the following additional
items in the determination of scientific and technical merit, but will not give
separate scores for these items.

Protections
for Human Subjects. For research that
involves human subjects but does not involve one of the six categories of
research that are exempt under 45 CFR Part 46, the committee will evaluate the
justification for involvement of human subjects and the proposed protections
from research risk relating to their participation according to the following five
review criteria: 1) risk to subjects, 2) adequacy of protection against risks,
3) potential benefits to the subjects and others, 4) importance of the
knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research
that involves human subjects and meets the criteria for one or more of
the six categories of research that are exempt under 45 CFR Part 46, the
committee will evaluate: 1) the justification for the exemption, 2) human
subjects involvement and characteristics, and 3) sources of materials.

Inclusion
of Women, Minorities, and Children. When the
proposed project involves clinical research, the committee will evaluate the
proposed plans for inclusion of minorities and members of both genders, as well
as the inclusion of children.

Vertebrate
Animals. The committee will evaluate the involvement
of live vertebrate animals as part of the scientific assessment according to
the following five points: 1) proposed use of the animals, and species,
strains, ages, sex, and numbers to be used; 2) justifications for the use of
animals and for the appropriateness of the species and numbers proposed; 3)
adequacy of veterinary care; 4) procedures for limiting discomfort, distress,
pain and injury to that which is unavoidable in the conduct of scientifically
sound research including the use of analgesic, anesthetic, and tranquilizing
drugs and/or comfortable restraining devices; and 5) methods of euthanasia and
reason for selection if not consistent with the AVMA Guidelines on Euthanasia.

Resubmission
Applications. When reviewing a Resubmission application
(formerly called an amended application), the committee will evaluate the
application as now presented, taking into consideration the responses to
comments from the previous scientific review group and changes made to the
project.

Renewal
Applications. When reviewing a Renewal application
(formerly called a competing continuation application), the committee will
consider the progress made in the last funding period.

Revision
Applications. When reviewing a Revision application
(formerly called a competing supplement application), the committee will
consider the appropriateness of the proposed expansion of the scope of the
project. If the Revision application relates to a specific line of investigation
presented in the original application that was not recommended for approval by
the committee, then the committee will consider whether the responses to
comments from the previous scientific review group are adequate and whether
substantial changes are clearly evident.

Biohazards. Reviewers will assess whether materials or procedures
proposed are potentially hazardous to research personnel and/or the
environment, and if needed, determine whether adequate protection is proposed.

Additional
Review Considerations

As applicable
for the project proposed, reviewers will address each of the following items,
but will not give scores for these items and should not consider them in
providing an overall impact/priority score.

Budget
and Period Support. Reviewers will consider
whether the budget and the requested period of support are fully justified and
reasonable in relation to the proposed research.

Select
Agents Research. Reviewers will assess the information
provided in this section of the application, including 1) the Select Agent(s)
to be used in the proposed research, 2) the registration status of all entities
where Select Agent(s) will be used, 3) the procedures that will be used to
monitor possession use and transfer of Select Agent(s), and 4) plans for
appropriate biosafety, biocontainment, and security of the Select Agent(s).

Applications
from Foreign Organizations. Reviewers
will assess whether the project presents special opportunities for furthering
research programs through the use of unusual talent, resources, populations, or
environmental conditions that exist in other countries and either are not
readily available in the United States or augment existing U.S. resources.

Undergo
a selection process in which only those applications deemed to have the
highest scientific and technical merit, generally the top half of
applications under review, will be discussed and assigned an
impact/priority score;

Receive
a written critique; and

Receive
a second level of review by the appropriate national
advisory council or board.

Applications submitted in response to this funding
opportunity will compete for available funds with all other recommended
applications

3. Anticipated Announcement and Award Dates

Not Applicable

Section
VI. Award Administration Information

1.
Award Notices

After the peer review of the application
is completed, the PD/PI will be able to access his or her Summary Statement
(written critique) via the NIH eRA Commons.

A formal notification in the form of a Notice of Award
(NoA) will be provided to the applicant organization. The NoA signed by the
grants management officer is the authorizing document. Once all administrative
and programmatic issues have been resolved, the NoA will be generated via email
notification from the awarding component to the grantee business official.

Selection of an application for award is not an
authorization to begin performance. Any costs incurred before receipt of the
NoA are at the recipient's risk. These costs may be reimbursed only to the
extent considered allowable pre-award costs. See Section
IV.5., “Funding Restrictions.”

A final progress report, invention statement,
and Financial Status Report are required when an award is relinquished when a
recipient changes institutions or when an award is terminated.

Section
VII. Agency Contacts

We
encourage your inquiries concerning this funding opportunity and welcome the
opportunity to answer questions from potential applicants. Inquiries may fall
into three areas: scientific/research (program), peer review, and financial or
grants management issues:

Human Subjects
Protection:Federal regulations (45 CFR 46) require that
applications and proposals involving human subjects must be evaluated with
reference to the risks to the subjects, the adequacy of protection against
these risks, the potential benefits of the research to the subjects and others,
and the importance of the knowledge gained or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).

Data and Safety
Monitoring Plan:Data and safety
monitoring is required for all types of clinical trials, including physiologic
toxicity and dose-finding studies (Phase I); efficacy studies (Phase II);
efficacy, effectiveness and comparative trials (Phase III). Monitoring should
be commensurate with risk. The establishment of data and safety monitoring
boards (DSMBs) is required for multi-site clinical trials involving
interventions that entail potential risks to the participants (“NIH Policy for
Data and Safety Monitoring,” NIH Guide for Grants and Contracts, https://grants.nih.gov/grants/guide/notice-files/not98-084.html).

Sharing
Research Data:Investigators
submitting an NIH application seeking $500,000 or more in direct costs in any
single year are expected to include a plan for data sharing or state why this
is not possible (https://grants.nih.gov/grants/policy/data_sharing).Investigators should
seek guidance from their institutions, on issues related to institutional
policies and local institutional review board (IRB) rules, as well as local,
State and Federal laws and regulations, including the Privacy Rule.

Policy for Genome-Wide
Association Studies (GWAS):NIH is interested in advancing genome-wide association
studies (GWAS) to identify common genetic factors that influence health and
disease through a centralized GWAS data repository. For the purposes of this
policy, a genome-wide association study is defined as any study of genetic
variation across the entire human genome that is designed to identify genetic
associations with observable traits (such as blood pressure or weight), or the
presence or absence of a disease or condition. All applications, regardless of
the amount requested, proposing a genome-wide association study are expected to
provide a plan for submission of GWAS data to the NIH-designated GWAS data
repository, or provide an appropriate explanation why submission to the repository
is not possible. Data repository management (submission and access) is governed
by the Policy for Sharing of Data Obtained in NIH Supported or Conducted
Genome-Wide Association Studies, NIH Guide NOT-OD-07-088.
For additional information, see https://grants.nih.gov/grants/gwas/.

Sharing of Model Organisms:NIH is committed to support efforts that encourage
sharing of important research resources including the sharing of model
organisms for biomedical research (see https://grants.nih.gov/grants/policy/model_organism/index.htm).
At the same time the NIH recognizes the rights of grantees and contractors to
elect and retain title to subject inventions developed with Federal funding
pursuant to the Bayh-Dole Act (see the NIH
Grants Policy Statement. Beginning October 1, 2004, all investigators
submitting an NIH application or contract proposal are expected to include in
the application/proposal a description of a specific plan for sharing and
distributing unique model organism research resources generated using NIH
funding or state why such sharing is restricted or not possible. This will
permit other researchers to benefit from the resources developed with public
funding. The inclusion of a model organism sharing plan is not subject to a
cost threshold in any year and is expected to be included in all applications
where the development of model organisms is anticipated.

Access to Research Data through the Freedom of
Information Act:The Office of Management and Budget (OMB) Circular
A-110 has been revised to provide access to research data through the Freedom
of Information Act (FOIA) under some circumstances. Data that are: (1) first
produced in a project that is supported in whole or in part with Federal funds;
and (2) cited publicly and officially by a Federal agency in support of an
action that has the force and effect of law (i.e., a regulation) may be
accessed through FOIA. It is important for applicants to understand the basic
scope of this amendment. NIH has provided guidance at https://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.
Applicants may wish to place data collected under this funding opportunity in a
public archive, which can provide protections for the data and manage the
distribution for an indefinite period of time. If so, the application should
include a description of the archiving plan in the study design and include
information about this in the budget justification section of the application.
In addition, applicants should think about how to structure informed consent
statements and other human subjects procedures given the potential for wider
use of data collected under this award.

Inclusion of Women And Minorities in Clinical
Research:It is the policy of the NIH that women and members of
minority groups and their sub-populations must be included in all NIH-supported
clinical research projects unless a clear and compelling justification is
provided indicating that inclusion is inappropriate with respect to the health
of the subjects or the purpose of the research. This policy results from the
NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All
investigators proposing clinical research should read the "NIH Guidelines
for Inclusion of Women and Minorities as Subjects in Clinical Research” (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html);
a complete copy of the updated Guidelines is available at https://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm.
The amended policy incorporates: the use of an NIH definition of clinical
research; updated racial and ethnic categories in compliance with the new OMB
standards; clarification of language governing NIH-defined Phase III clinical
trials consistent with the SF424 (R&R) application; and updated roles and
responsibilities of NIH staff and the extramural community. The policy
continues to require for all NIH-defined Phase III clinical trials that: a) all
applications or proposals and/or protocols must provide a description of plans
to conduct analyses, as appropriate, to address differences by sex/gender
and/or racial/ethnic groups, including subgroups if applicable; and b)
investigators must report annual accrual and progress in conducting analyses,
as appropriate, by sex/gender and/or racial/ethnic group differences.

Inclusion of Children as Participants in Clinical
Research:The NIH maintains a policy that children (i.e.,
individuals under the age of 21) must be included in all clinical research,
conducted or supported by the NIH, unless there are scientific and ethical
reasons not to include them.

Required Education on the Protection of Human Subject
Participants:NIH policy requires education on the protection of
human subject participants for all investigators submitting NIH applications
for research involving human subjects and individuals designated as key
personnel. The policy is available at https://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

NIH Public Access Policy Requirement:
In accordance with the NIH Public Access Policy,investigators
funded by the NIH must submit or have submitted for them to the
National Library of Medicine’s PubMed Central (see http://www.pubmedcentral.nih.gov/), an
electronic version of their final, peer-reviewed manuscripts upon acceptance for publication, to be made publicly available no
later than 12 months after the official date of publication. The
NIH Public Access Policy is available at (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-033.html).For more information, see the Public
Access webpage at http://publicaccess.nih.gov/.

Standards for Privacy of Individually Identifiable
Health Information:The Department
of Health and Human Services (HHS) issued final modification to the
"Standards for Privacy of Individually Identifiable Health
Information", the "Privacy Rule", on August 14, 2002. The
Privacy Rule is a federal regulation under the Health Insurance Portability and
Accountability Act (HIPAA) of 1996 that governs the protection of individually
identifiable health information, and is administered and enforced by the HHS
Office for Civil Rights (OCR).

Decisions about
applicability and implementation of the Privacy Rule reside with the researcher
and his/her institution. The OCR website (http://www.hhs.gov/ocr/)
provides information on the Privacy Rule, including a complete Regulation Text
and a set of decision tools on "Am I a covered entity?" Information
on the impact of the HIPAA Privacy Rule on NIH processes involving the review,
funding, and progress monitoring of grants, cooperative agreements, and
research contracts can be found at https://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

URLs
in NIH Grant Applications or Appendices:
All applications and proposals
for NIH funding must be self-contained within specified page limitations. For
publications listed in the appendix and/or Progress report, Internet addresses
(URLs) or PubMed Central (PMC) submission identification numbers must be used
for publicly accessible on-line journal articles. Publicly accessible
on-line journal articles or PMC articles/manuscripts accepted for publication
that are directly relevant to the project may be included only as URLs or PMC submission identification numbers accompanying the full reference
in either the Bibliography & References Cited section, the Progress Report
Publication List section, or the Biographical Sketch section of the NIH grant
application. A URL or PMC submission identification number citation may be
repeated in each of these sections as appropriate. There is no limit to the
number of URLs or PMC submission identification numbers that can be cited.

Healthy People 2010:The Public
Health Service (PHS) is committed to achieving the health promotion and disease
prevention objectives of "Healthy People 2010," a PHS-led national
activity for setting priority areas. This FOA is related to one or more of the
priority areas. Potential applicants may obtain a copy of "Healthy People
2010" at http://www.health.gov/healthypeople.

Authority and
Regulations:This program is described in
the Catalog
of Federal Domestic Assistance athttp://www.cfda.gov/ and is not subject to the
intergovernmental review requirements of Executive
Order 12372. Awards are made under the authorization of Sections 301 and 405 of
the Public Health Service Act as amended (42 USC 241 and 284) and under Federal
Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92. All awards are subject to the terms and conditions, cost principles,
and other considerations described in the NIH Grants
Policy Statement.

The PHS strongly
encourages all grant recipients to provide a smoke-free workplace and
discourage the use of all tobacco products. In addition, Public Law 103-227,
the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in
some cases, any portion of a facility) in which regular or routine education,
library, day care, health care, or early childhood development services are
provided to children. This is consistent with the PHS mission to protect and
advance the physical and mental health of the American people.

Loan
Repayment Programs:NIH encourages
applications for educational loan repayment from qualified health professionals
who have made a commitment to pursue a research career involving clinical,
pediatric, contraception, infertility, and health disparities related areas.
The LRP is an important component of NIH's efforts to recruit and retain the
next generation of researchers by providing the means for developing a research
career unfettered by the burden of student loan debt. Note that an NIH grant is
not required for eligibility and concurrent career award and LRP applications
are encouraged. The periods of career award and LRP award may overlap providing
the LRP recipient with the required commitment of time and effort, as LRP
awardees must commit at least 50% of their time (at least 20 hours per week
based on a 40 hour week) for two years to the research. For further
information, please see: http://www.lrp.nih.gov/.